title: Sibutramine effect on metabolic control of obese patients with type 2 diabetes mellitus treated with pioglitazone.
abstract: Thiazolidinediones are supposed to be the pharmacologic agents that more physiologically fight the insulin resistance, but a possible adverse effect may be a weight increase. The aim of the study was to test the efficacy and tolerability of sibutramine on the metabolic effect of pioglitazone in obese patients with type 2 diabetes mellitus. All enrolled patients were required to have been diagnosed as being diabetic for at least 6 months and did not have glycemic control with diet and oral hypoglycemic agents such as sulfonylureas or metformin, both to the maximum tolerated dose. After a run-in period in which the eligible patients took a fixed dose of pioglitazone (30 mg/d), the patients were randomized to receive also sibutramine (10 mg/d) or placebo for 6 months. We assessed body mass index, hemoglobin A(1c) (HbA(1c)), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), postprandial plasma insulin (PPI), lipid profile, lipoprotein parameters, and lipoprotein (a) at baseline and after 3 and 6 months. No body mass index change was observed after 3 and 6 months in the pioglitazone + placebo (pp) group. Significant decrease was present in the pioglitazone + sibutramine (ps) group after 3 (P < .05) and 6 months (P < .01) compared with the baseline values, and this variation was significant (P < .05) between groups. A significant HbA(1c) decrease was observed after 3 (P < .05) and 6 months (P < .01) in both groups with respect to the baseline values. There was no difference in HbA(1c) value between the 2 groups. No FPG, PPG, FPI, PPI, and homeostasis model assessment index change was observed at 3 months, whereas a significant decrease was present after 6 months (P < .05), in both groups with respect to the baseline values. There was no difference in FPG, PPG, FPI, PPI, and homeostasis model assessment index value between the pp and ps groups. No significant low-density lipoprotein cholesterol change was observed at 3 months, whereas a significant decrease was present after 6 months (P < .05), in both groups with respect to the baseline values. There was no difference in low-density lipoprotein cholesterol value between the pp and ps groups. No triglyceride variation was present at 3 and 6 months in the pp group and at 3 months in the ps group, whereas a significant decrease was observed at 6 months (P < .05) in the ps group with respect to the baseline values. There was no difference in triglyceride value between both groups. No high-density lipoprotein cholesterol, apolipoprotein A-I, apolipoprotein B, and lipoprotein (a) changes were present in both groups with respect to the baseline values. Sibutramine appears to be a tolerable and efficacious drug when added to pioglitazone for the global management of obese diabetic patients.
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, 19-27100 Pavia, Italy. giuseppe.derosa@unipv.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Derosa
authors.forename: Angela
authors.initials: A
authors.lastname: D'Angelo
authors.forename: Sibilla A T
authors.initials: SA
authors.lastname: Salvadeo
authors.forename: Ilaria
authors.initials: I
authors.lastname: Ferrari
authors.forename: Alessia
authors.initials: A
authors.lastname: Gravina
authors.forename: Elena
authors.initials: E
authors.lastname: Fogari
authors.forename: Pamela
authors.initials: P
authors.lastname: Maffioli
authors.forename: Arrigo F G
authors.initials: AF
authors.lastname: Cicero
mesh_terms: D001067:Appetite Depressants / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D003503:Cyclobutanes / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D001067:Appetite Depressants; D001786:Blood Glucose; D008076:Cholesterol, HDL; D003503:Cyclobutanes; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D045162:Thiazolidinediones; C058254:sibutramine; D000077205:Pioglitazone